Antimutagenic effect of ellagic acid and its effect on the immune response in mice

Using the Ames bacterial mutagenicity test and an in vivo micronucleus test, we investigated the antigenotoxic effect of ellagic acid on the genotoxicity of three mutagens: amino-methylimidazo-quinoline (IQ), aflatoxin B1 (AFB1), and N-nitroso-N-methylurea (MNU). Ellagic acid is a naturally occurring phenolic compound which is found in a variety of soft fruits and vegetables. The effect of this compound on the immunosuppressive activity of mutagens was followed in vivo by the chemiluminescence test. In the Ames assay, ellagic acid at concentrations of 300 and 30 μg/plate demonstrably inhibits the mutagenic activity of two indirect mutagens: IQ and AFB1. The concentration of 300 μg/plate had the strongest effect on mutagenicity of all concentrations of IQ in strain TA98 of Salmonella typhimurium, whereas in strain TA100 concentration of 30 μg per dish of ellagic acid was more effective than 300 μg per plate. Also in combination with different concentrations of AFB1, ellagic acid proved to be a strong antimutagen. In this case the lower of the two effective concentrations - 30 μg/plate - had a much greater antimutagenic effect on both strains tested than 300 μg/plate. In combination with the direct mutagen MNU, ellagic acid did not show any marked antimutagenic effect at most of the concentrations tested in strain TA100. Only the highest concentrations of ellagic acid reduced the mutagenic effect of MNU weakly and only in combination with two lower concentrations of MNU. In the micronucleus test, three-day oral application of ellagic acid prior to the applicaton of AFB1, IQ, or MNU, respectively, markedly reduced the numbers of micronuclei induced by these three mutagens in polychromatophilic erythrocytes of mice. Chemiluminescence test with mouse granulocytes proved that ellagic acid not only prevents the inhibitory effects of mutagens on free oxygen radicals and hydrogen peroxide production, but that this production is stimulated by ellagic acid in combination with mutagens even to a greater extent than by ellagic acid alone. From these results we can deduce that ellagic acid repairs strong immunosuppressive effects of all mutagens applied.